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ForumsPublic SquareStarted this morning and already overthinking everything — my results so far

Started this morning and already overthinking everything — my results so far

hans_munich Wed, Sep 11, 2024 at 11:16 PM 56 replies 2,355 viewsPage 1 of 12
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hans_munich
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Sep 11, 2024 at 11:16 PM#1

My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my material.

So the question, as narrowly as I can put it: how to read a result like this without either dismissing it or over-reading it, since the summaries all read like press releases.

Practical detail welcome, however dull — the duller the better.

9 12kevin_tulsa, Dr.PainCLE, mike_mealprep and 6 others
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CarlaRPh_TPA
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Sep 11, 2024 at 11:22 PM#2

Taking the question as asked, rather than the general version of it. Read four things before the headline number. The population, because trial populations are selected and supported in ways that real cohorts are not. The comparator, because "better than placebo" and "better than the current standard" are different claims and get reported identically. The primary endpoint as pre-registered, because a secondary endpoint promoted after the fact is a hypothesis rather than a finding. And the completion rate, because a large effect in the half of participants who finished is a different result from a large effect in everybody enrolled.

10 13ricardo_MIA, BrianDallas92, labquiet_amy and 7 others
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AmyNC_wife
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Sep 11, 2024 at 11:28 PM#3
CarlaRPh_TPA said:
Read four things before the headline number.

Forest plot interpretation for the the trial evidence meta-analysis: when reading the pooled estimate, pay attention to:

  1. Point estimate (HR/RR/OR) — center of the diamond
  2. Confidence interval width — precision of the estimate
  3. I² statistic — heterogeneity across studies
  4. Individual study weights — are results driven by one large trial?
  5. Prediction interval — range of plausible true effects in future settings

The the trial evidence meta-analysis shows a pooled RR of 0.75 (95% CI 0.65-0.90), I²=48%. This is a robust and consistent effect.

Last edited: Sep 12, 2024 at 12:28 AM
11 14PharmD_Rodriguez, julia.endo, JessicaM_2024 and 8 others
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bbq_ray_KC
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Sep 11, 2024 at 11:34 PM#4
hans_munich said:
My own curve sits about four points below the published mean and I spent two months assuming that meant something was wrong with me or with my…

This matches mine closely enough to be worth saying so. Relative and absolute effects need reading together. A 20% relative reduction on a high baseline risk is a large absolute benefit; the same relative figure on a low baseline risk is a small one, and press summaries almost always quote the relative number because it is bigger.

Last edited: Sep 12, 2024 at 1:34 AM
12 15WendyG_ATL, SaraMom3, Dr.MetabolicMD and 9 others
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julia.endo
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Sep 12, 2024 at 12:05 AM#5

Clinical perspective, offered as context rather than as advice.

Bayesian meta-analysis perspective on the trial evidence: traditional frequentist meta-analyses report point estimates and confidence intervals. Bayesian approaches provide probability distributions that are more intuitive for clinical decision-making.

For example: "There is a 98.5% probability that semaglutide 2.4mg produces >10% weight loss vs placebo" is more actionable than "RR 3.4, 95% CI 2.8-4.1, p<0.001."

The the trial evidence evidence is strong under both frameworks, but Bayesian analysis better communicates the degree of certainty for individual patient counseling.

Last edited: Sep 12, 2024 at 6:05 AM
13 16chris_chi24, tampaLisa73, KarenAZ_mom and 10 others
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